The above compound of the formula (I) is an important key intermediate for the synthesis of a drug having potent calcium channel blocking activity and has been clinically used as an effective antianginal and antihypertensive agent whose generic name is Diltiazem (Merck Index, X Edition N, 3189, page 466). The compound of the formula (II) has two asymmetric carbon atoms, at the positions 2 and 3. Thus, it can have two types of stereoisomers, namely the threo and the erythro forms. The threo form has two optical isomers. Normally it is obtained as a racemic mixture, but by reacting with an optically active .alpha.-methylbenzylamine of the formula (III) in a solvent the two diastereomer salts can be optically resolved using their differences in a solubility. The compound of the formula (I) is currently prepared by the optical resolution of (2RS,3RS)(2-aminophenylthio)-2-hydroxy-3-(4'-methoxyphenyl)propionic acid of the formula (II) treating it with half equimolar amount of optically active (+).alpha.-methylbenzylamine represented by the general formula (III) as resolving agent and alkali in the presence of a polar solvent as described in Example 1. The requisite (+).alpha.-methylbenzylamine is commercially available.
Inone et al (Yakugaku Zasshi, 93, 279, 1973) reported by the optical resolution of (.+-.) compound of the formula (II) using cinchonidine. The less soluble cinchonidine salt of the formula (II) however, was the unwanted (2R,3R)isomer and the desired (2S,3S)isomer was obtained from the mother liquor. This process has the drawback of the requirement of a large quantity of expensive cinchonidine.
The main object of the present invention is to provide an improved process for the optical resolution of (2RS,3RS)-3-(2-aminophenylthio)-2-hydroxy-3-(4'-methoxyphenyl)propionic acid which overcomes the drawbacks of the hitherto known process.